Identification of the absorbed constituents and metabolites of Huangqi Guizhi Wuwu decoction by ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Huangqi Guizhi Wuwu decoction (HGWWD) is a widely used traditional Chinese medicine (TCM) preparation for the treatment of ischemic stroke and diabetes peripheral neuropathy. However, the material basis for the efficacy of HGWWD remains unclear. In this study, a rapid, sensitive and selective ultrahigh-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) method was developed to separate and identify the absorbed components and metabolites of HGWWD in rat plasma after oral administration for the first time. By comparing the retention time, high-resolution mass spectrometry primary and secondary mass spectrometry data of blank plasma and drug-containing plasma, a total of 42 constituents, including 24 prototype compounds and 18 metabolites, were identified or tentatively characterized. The results indicated that monoterpenes, flavonoids, organic acids, amino acids, gingerols and alkaloids were main prototype compounds in rat plasma, and flavonoid-related metabolites, organic acid-related metabolites and gingerol-related metabolites were major metabolites. It is concluded the developed UHPLC-Q-TOF-MS method with high sensitivity and resolution is suitable for identifying and characterizing the absorbed components and metabolites of HGWWD, and the results will provide important data for further study on the relationship between the chemical constituents and pharmacological activities of HGWWD.

Characterization of the Chemical Constituents in Radix gentianae by Ultra-High Performance Liquid Chromatography Coupled with Quadrupole Time-of-Flight Mass Spectrometry.

Radix gentianae (RG) is a traditional Chinese medicine used for the treatment of acute and chronic hepatitis in clinic. However, the chemical profile of RG is still unconfirmed, which hindered the progress of pharmacological study and clinical application. In this study, ultra-high performance liquid chromatography together with quadrupole time-of-flight mass spectrometry techniques were employed to separate and characterize the chemical constituents in RG. Under the optimized conditions, a total of 60 compounds were rapidly identified or tentatively characterized. Results indicated that iridoid glucosides, flavonoids, organic acids, amino acids, saccharides and nucleosides were major constituents in RG. It is concluded the established method can help to clarify the substance basis and provide useful information for ascertaining the bioactive constituents and action mechanism of RG.

Characterization of chemical constituents in Huangqi Guizhi Wuwu decoction using ultra-high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Huangqi Guizhi Wuwu decoction (HGWWD) is a classic traditional Chinese medicine prescription for the treatment of ischemic stroke, etc. However, the material basis of its efficacy remains unclear, seriously affecting drug development and clinical applications. In the present study, an ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry method was developed to separate and identify the chemical components of HGWWD. A total of 81 compounds were identified and tentatively characterized. Eight compounds were accurately identified by comparing the retention time and mass spectrometry data with those of reference substances, the remaining compounds were characterized by comparing the mass spectrometry data and reference information. Based on the results of compound attribution, 35 compounds were from Astragali Radix, six compounds were from Cinnamomi Ramulus, 23 compounds were from Paeoniae Radix Alba, eight compounds were from Zingiberis Rhizoma Recens and nine compounds were from Jujubae Fructus. The results showed that monoterpenoids, flavonoids, organic acids, triterpenes, amino acids, gingerols, alkaloids, and glycosides were the main chemical components of HGWWD. This analytical method is suitable for characterizing the chemical constituents of HGWWD, and the results provide important information for elucidating its pharmacodynamic material basis and mechanism of action.

Toward an early clinical diagnosis of MM2-type sporadic Creutzfeldt-Jakob disease.

OBJECTIVE: To assess the proportion of clinically diagnosed MM2-type sporadic Creutzfeldt-Jakob disease (sCJD) in a Chinese cohort, describe the clinical features of MM2-cortical (MM2C) and MM2-thalamic (MM2T) type sCJD to improve the early detection of MM2-type sCJD. METHODS: A total of 209 patients with sCJD admitted to the Xuanwu Hospital between February 2012 and August 2022 were reviewed. The patients were classified into probable MM2C, MM2T-type sCJD, and other types of sCJD according to current clinical diagnostic criteria. Clinical and ancillary data were compared between the groups. RESULTS: Fifty-one (24.4%) patients were clinically diagnosed with MM2-type sCJD, of which 44 were diagnosed with MM2C-type sCJD and 7 with MM2T-type sCJD. In the absence of RT-QuIC, 27 (61.3%) patients of MM2C-type sCJD did not meet the US CDC sCJD criteria for possible sCJD on admission, even though the mean period from onset to admission was 6.0 months. However, all of these patients had cortical hyperintensity on DWI. Compared to the other types of sCJD, MM2C-type sCJD was associated with slower disease progression and the absence of the typical clinical features of sCJD; the MM2T-type sCJD group had a higher proportion of males, earlier age of onset, longer duration of disease, and a higher incidence of bilateral thalamic hypometabolism/hypoperfusion. INTERPRETATION: In the absence of multiple typical sCJD symptoms within 6 months, the presence of cortical hyperintensity on DWI should raise concerns for MM2C-type sCJD after excluding other etiologies. Bilateral thalamic hypometabolism/hypoperfusion may be more helpful in the clinical diagnosis of MM2T-type sCJD.

Metabolite profiles of Gansuibanxia decoction in rat plasma and urine by UHPLC-Q-TOF/MS analysis.

Gansuibanxia decoction (GSBXD), a traditional Chinese medicine (TCM) formula with 2000 years of history, has good efficacies on treating cancerous ascites, pleural effusion, etc. However, little is known about its metabolite profiles owing to the lack of in vivo studies. In this study, we explored the prototypes and metabolites of GSBXD in rat plasma and urine using UHPLC-Q-TOF/MS technology. A total of 82 GSBXD-related xenobiotic bioactive components (38 prototypes and 44 metabolites) were confirmed or tentatively characterized, including 32 prototypes and 29 metabolites in plasma, and 25 prototypes and 29 metabolites in urine. The results showed that the bioactive components absorbed in vivo mainly contained diterpenoids, triterpenoids, flavonoids and monoterpene glycosides. Both phase I reactions (methylation, reduction, demethylation, hydrolysis, hydroxylation and oxidation) and phase II reactions (glucuronidation and sulfation) were involved in the metabolism of GSBXD in vivo. This study will provide a foundation for the quality control, pharmacological study and clinical application of GSBXD.

Thalamic-insomnia phenotype in E200K Creutzfeldt-Jakob disease: A PET/MRI study.

BACKGROUND: Insomnia and thalamic involvement were frequently reported in patients with genetic Creutzfeldt-Jakob disease (gCJD) with E200K mutations, suggesting E200K might have discrepancy with typical sporadic CJD (sCJD). The study aimed to explore the clinical and neuroimage characteristics of genetic E200K CJD patients by comprehensive neuroimage analysis. METHODS: Six patients with gCJD carried E200K mutation on Prion Protein (PRNP) gene, 13 patients with sporadic CJD, and 22 age- and sex-matched normal controls were enrolled in the study. All participants completed a hybrid positron emission tomography/magnetic resonance imaging (PET/MRI) examination. Signal intensity on diffusion-weighted imaging (DWI) and metabolism on PET were visually rating analyzed, statistical parameter mapping analysis was performed on PET and 3D-T1 images. Clinical and imaging characteristics were compared between the E200K, sCJD, and control groups. RESULTS: There was no group difference in age or gender among the E200K, sCJD, and control groups. Insomnia was a primary complaint in patients with E200K gCJD (4/2 versus 1/12, p = 0.007). Hyperintensity on DWI and hypometabolism on PET of the thalamus were observed during visual rating analysis of images in patients with E200K gCJD. Gray matter atrophy (uncorrected p < 0.001) and hypometabolism (uncorrected p < 0.001) of the thalamus were more pronounced in patients with E200K gCJD. CONCLUSION: The clinical and imaging characteristics of patients with gCJD with PRNP E200K mutations manifested as a thalamic-insomnia phenotype. PET is a sensitive approach to help identify the functional changes in the thalamus in prion disease.

[Optimization of formulation of paclitaxel nanosuspension encapsulated by erythrocyte membrane based on Box-Behnken method].

In view of the longevity and innate immune escape of red blood cells, this study designed the red blood cell membrane-coated paclitaxel nanosuspension [RBC-(PTX)NS] and investigated its physicochemical properties and antitumor effect in vitro. Paclitaxel nanosuspension [(PTX)NS] was prepared by ultrasonic precipitation and then RBC-(PTX)NS by ultrasonic coating. The formulation of(PTX)NS was optimized with Box-Behnken method and indexes of particle diameter, zeta potential, and stability. The morphology, particle diameter, stability, in vitro dissolution, and antitumor effect of(PTX)NS and RBC-(PTX)NS were characterized. The results showed that the particle diameter and zeta potential were(129.38±0.92) nm and(-22.41±0.48) mV, respectively, for the optimized(PTX)NS, while(142.5±0.68) nm and(-29.85±0.53) mV, respectively, for RBC-(PTX)NS. Under the transmission electron microscope,(PTX)NS was spherical and RBC-(PTX)NS had obvious core-shell structure. RBC-(PTX)NS remained stable for 5 days at 4 ℃. The in vitro dissolution test demonstrated that the cumulative release rate of RBC-(PTX)NS reached 79% within 20 min, which was significantly higher than that(25%) of(PTX)NS(P<0.05). As evidenced by MTT assay, RBC-(PTX)NS highly inhibited the proliferation of HepG2 cells in a dose-dependent manner. The cell membrane-coated nano-preparation preparation method is simple and reproducible. It improves the solubility of PTX and endows RBC-(PTX)NS with higher stability and stronger cytotoxicity. Thus, it is a new method for the delivery of PTX via nanocrystallization.

Specific structuro-metabolic pattern of thalamic subnuclei in fatal familial insomnia: A PET/MRI imaging study.

BACKGROUND: Dysfunction of the thalamus has been proposed as a core mechanism of fatal familial insomnia. However, detailed metabolic and structural alterations in thalamic subnuclei are not well documented. We aimed to address the multimodal structuro-metabolic pattern at the level of the thalamic nuclei in fatal familial insomnia patients, and investigated the clinical presentation of primary thalamic alterations. MATERIALS AND METHODS: Five fatal familial insomnia patients and 10 healthy controls were enrolled in this study. All participants underwent neuropsychological assessments, polysomnography, electroencephalogram, and cerebrospinal fluid tests. MRI and fluorodeoxyglucose PET were acquired on a hybrid PET/MRI system. Structural and metabolic changes were compared using voxel-based morphometry analyses and standardized uptake value ratio analyses, focusing on thalamic subnuclei region of interest analyses. Correlation analysis was conducted between gray matter volume and metabolic decrease ratios, and clinical features. RESULTS: The whole-brain analysis showed that gray matter volume decline was confined to the bilateral thalamus and right middle temporal pole in fatal familial insomnia patients, whereas hypometabolism was observed in the bilateral thalamus, basal ganglia, and widespread cortices, mainly in the forebrain. In the regions of interest analysis, gray matter volume and metabolism decreases were prominent in bilateral medial dorsal nuclei, anterior nuclei, and the pulvinar, which is consistent with neuropathological and clinical findings. A positive correlation was found between gray matter volume and metabolic decrease ratios. CONCLUSIONS: Our study revealed specific structuro-metabolic pattern of fatal familial insomnia that demonstrated the essential roles of medial dorsal nuclei, anterior nuclei, and pulvinar, which may be a potential biomarker in diagnosis. Also, primary thalamic subnuclei alterations may be correlated with insomnia, neuropsychiatric, and autonomic symptoms sparing primary cortical involvement.

Thermlanseedlines A-G, seven thermopsine-based alkaloids with antiviral and insecticidal activities from the seeds of Thermopsis lanceolata R. Br.

Seven undescribed thermopsine-based alkaloids (1-7), including one undescribed biogenetically related intermediate (7), were isolated from the seeds of Thermopsis lanceolata R. Br. Compound 1 possessed a 6/6-6 tricyclic skeleton, while compounds 2-6 represented three rare dimerization patterns constructed by quinolizidine alkaloids. Their structures were elucidated by comprehensive spectroscopic data analysis as well as ECD calculations. Biologically, compound 6 displayed significant anti-Tomato spotted wilt virus (TSWV) activity compared with the positive control ningnanmycin. Moreover, compound 1 exhibited good insecticidal activity against Aphis fabae with LC50 value of 25.2 mg/L.

Luteolin relieves lung cancer-induced bone pain by inhibiting NLRP3 inflammasomes and glial activation in the spinal dorsal horn in mice.

BACKGROUND: Bone cancer pain (BCP) is one of the most severe complications in cancer patients. However, the pharmacological therapeutic approaches are limited. Luteolin, a major component of flavones, is widely distributed in plants and plays a critical role in the antinociceptive effects, but whether luteolin could alleviate cancer pain and its underlying mechanisms are not known. HYPOTHESIS/PURPOSE: This study investigated the molecular mechanisms by which luteolin reduced BCP. METHODS: Behavioral, pharmacological, immunohistochemical, and biochemical approaches were used to investigate the effect of luteolin on BCP. RESULTS: Luteolin treatment ameliorated Lewis lung cancer (LLC)-induced bone pain in mice in a dose-dependent manner. Luteolin treatment could inhibit the activation of neurons, glial cells, and NOD-like receptor protein 3 (NLRP3) inflammasomes in the dorsal spinal cord in the BCP mouse model. Furthermore, phosphorylated p-38 mitogen-activated protein kinase (MAPK) in the spinal dorsal horn (SDH) was suppressed by luteolin treatment that could influence the analgesic and glial inhibition effects of luteolin. CONCLUSION: Our results demonstrated that luteolin inhibited neuroinflammation by obstructing glial cell and NLRP3 inflammasome activation via modulating p38 MAPK activity in SDH, ultimately improving LLC-induced BCP.

Neuronal Yin Yang1 in the prefrontal cortex regulates transcriptional and behavioral responses to chronic stress in mice.

Although the synaptic alterations associated with the stress-related mood disorder major depression has been well-documented, the underlying transcriptional mechanisms remain poorly understood. Here, we perform complementary bulk nuclei- and single-nucleus transcriptome profiling and map locus-specific chromatin interactions in mouse neocortex to identify the cell type-specific transcriptional changes associated with stress-induced behavioral maladaptation. We find that cortical excitatory neurons, layer 2/3 neurons in particular, are vulnerable to chronic stress and acquire signatures of gene transcription and chromatin structure associated with reduced neuronal activity and expression of Yin Yang 1 (YY1). Selective ablation of YY1 in cortical excitatory neurons enhances stress sensitivity in both male and female mice and alters the expression of stress-associated genes following an abbreviated stress exposure. These findings demonstrate how chronic stress impacts transcription in cortical excitatory neurons and identify YY1 as a regulator of stress-induced maladaptive behavior in mice.

[Total flavonoids of Drynariae Rhizoma regulates ER-p38 MAPK signaling pathway to improve scopolamine-induced learning and memory impairments in model mice].

This study intended to explore the effect and mechanism of total flavonoids of Drynariae Rhizoma in improving scopola-mine-induced learning and memory impairments in model mice. Ninety four-month-old Kunming(KM) mice were randomly divided into six groups. The ones in the model group and blank group were treated with intragastric administration of normal saline, while those in the medication groups separately received the total flavonoids of Drynariae Rhizoma, Kangnaoshuai Capsules, donepezil, as well as total flavonoids of Rhizoma Drynariae plus estrogen receptor(ER) blocker by gavage. The mouse model of learning and memory impairments was established via intraperitoneal injection of scopolamine. Following the measurement of mouse learning and memory abilities in Morris water maze test, the hippocampal ERß expression was detected by immunohistochemistry, and the expression levels of ERß and phosphorylated p38(p-p38) in the hippocampus and B-cell lymphoma 2(Bcl-2), Bcl-2-associated death promoter(Bad), and cysteinyl aspartate-specific protease-3(caspase-3) in the apoptotic system were assayed by Western blot. The contents of malondia-ldehyde(MDA), superoxide dismutase(SOD), and nitric oxide(NO) in the hippocampus were then determined using corresponding kits. Compared with the control group, the model group exhibited significantly prolonged incubation period, reduced frequency of cros-sing the platform, shortened residence time in the target quadrant, lowered ERß, Bcl-2 and SOD activity in the hippocampus, and increased p-p38/p38, Bad, caspase-3, MDA, and NO. Compared with the model group, the total flavonoids of Rhizoma Drynariae increased the expression of ERß and SOD in the hippocampus, down-regulated the expression of neuronal pro-apoptotic proteins, up-re-gulated the expression of anti-apoptotic proteins, and reduced p-p38/p38, MDA, and NO. The effects of total flavonoids of Drynariae Rhizoma on the above indexes were reversed by ER blocker. It has been proved that the total flavonoids of Drynariae Rhizoma obviously alleviate scopolamine-induced learning and memory impairments in mice, which may be achieved by regulating the neuronal apoptotic system and oxidative stress via the ER-p38 mitogen-activated protein kinase(ER-p38 MAPK) signaling pathway.

Tissue Distribution Study of Poloxamer188 in Rats by Ultra-High-Performance Liquid Chromatography Quadrupole Time of Flight/Mass Spectrometry with MSALL-Based Approach.

Poloxamer188 (PL188), as one of the most commonly used pharmaceutical excipients, has unique physicochemical properties and good biocompatibility, and so is playing an increasingly extensive role in the field of medicine. Currently, there are few studies on the tissue distribution of PL188 in vivo. In this study, the LC-MS method based on MSALL technique of quadrupole time of flight mass spectrometry for absolute quantitative analysis of poloxamer 188 in biological substrates was established for the first time. The tissue distribution of poloxamer188 in SD rats were studied using the established quantitative analysis method. To explore the distribution of PL188 in organs and tissues, PL188 was administered via rat tail vein at a dose of 5 mg/kg. Eight kinds of tissues including heart, liver, spleen, lung, kidney, stomach, muscle and brain of rats were collected at 0.25 h, 1 h and 4 h after administration. Tissue distributions showed the highest level was observed in kidney, then in stomach, which indicated PL188 mainly bioaccumulated in the kidney. This study can provide references for the further study of PL188.

Bibliometric analysis of phosphogypsum research from 1990 to 2020 based on literatures and patents.

The demand together with the urgency of phosphogypsum (PG) treatment will pose significant challenges for many countries. This research aims to explore the research progress of PG, including basic status, cooperation situation, research fields, and development trends, based on the Web of Science database through bibliometric analysis of publications (articles and patents) from 1990 to 2020. The results show that academic research on PG originated early, but the number of patents grew quickly. China is a global leader in terms of the number of publications and plays a significant role in international cooperation. The knowledge of PG has remained concentrated in the fields of natural radioactivity, cement paste backfilling, soil, crystal morphology, and synthetic gas. However, academic hotspots focus on the microstructure of chemical processes and various environmental impacts; patents and hot technologies are based on the production of refractory materials, ceramics, surface materials, cement mortar, and composite materials. The academic frontiers of PG will be centered on exploiting the methods of recovering rare earth elements from PG, the conditions of ion solidification/stabilization in PG, the impact of reaction conditions on product quality, and the reaction mechanism at the micro-level. The frontiers of patents need to focus on the improvement of manufacturing equipment, new wall materials, and chemically modified polymer materials. Envisaging the number of articles and patents to be published in the future, architectural research has a large room for improvement. This paper conducts an in-depth analysis of PG and provides information on the technological development prospects and opportunities, which is helpful for researchers engaged in PG management.

Screening of differential components of Gegenqinlian decoction and their comparative pharmacokinetics in normal and pyrexia rats using UHPLC-FT-ICR-MS and UHPLC-MS/MS.

UHPLC combined with Fourier-transform ion cyclotron resonance MS metabonomic approach was employed to screen the differential components between normal rats and yeast-induced pyrexia rats after an oral administration of Gegenqinlian decoction (GQLD). Nine compounds, namely puerarin, daidzein, baicalin, wogonoside, wogonin, berberine, palmatine, jateorhizine, and coptisine, were identified as differential components in the plasma. A rapid, sensitive, selective, and accurate UHPLC-MS method was developed and fully validated for the simultaneous determination of the screened components in rat plasma after an oral administration of GQLD. The values for the limit of quantification ranged from 0.025 to 5.0 ng/mL. The inter- and intra-day precision of all analytes was ≤10.7%, with an accuracy of ≤10.5%. Good extraction recovery and matrix effects were also obtained. The method was successfully applied to a comparative pharmacokinetic study of GQLD in normal and pyrexia rats. The results showed that the pharmacokinetic behavior of the analytes was changed in pyrexia rats compared to normal rats. These results could provide beneficial guidance for clinical applications of GQLD.

Omega-3 fatty acids improve flow-induced vasodilation by enhancing TRPV4 in arteries from diet-induced obese mice.

AIMS: Previous studies have shown the intake of omega-3 polyunsaturated fatty acids is associated with low rates of obesity and ischaemic pathologies. Omega-3 also have anti-inflammatory and plaque-stabilization effects and regulate vasodilation and constriction. However, there are few studies of the role of omega-3 in flow-induced vasodilation involving Ca2+-permeable ion channel TRPV4 in high-fat diet-induced obese (DIO) mouse. Here, we determined whether omega-3 protect against vascular dysfunction induced by a high-fat diet by enhancing TRPV4 activity and subsequently improving flow-mediated vasodilation. METHODS AND RESULTS: Flow-mediated vasodilation in second-order mesenteric arteries from mice was measured using a pressure myograph. The intracellular Ca2+ concentration in response to flow and GSK1016790A (a TRPV4 agonist) was measured by Fluo-4 fluorescence. Whole-cell current was measured by patch clamp. Cell membrane tether force was measured by atomic force microscopy. Impairment of flow-mediated vasodilation in arteries and Ca2+ influx in endothelial cells from DIO mice was restored by omega-3 treatment. The improved flow-induced vasodilation was inhibited by the TRPV4 antagonist HC067047 and in TRPV4-/- mice. Omega-3 treatment enhanced endothelial TRPV4 activity and altered cell membrane mechanic property, as indicated by enhanced GSK1016790A-induced Ca2+ influx and whole-cell current and altered membrane mean tether force in endothelial cells from DIO mice. CONCLUSION: Omega-3 improve vascular function by improving flow-induced vasodilation via enhancing TRPV4 activity in the endothelium of obese mice which may be related to improved cell membrane physical property. Activation of TRPV4 in endothelium plays an important role in the protective mechanisms of omega-3 against vascular dysfunction in obesity by improving flow-mediated vasodilation.

Antidepressive Effect of Arctiin by Attenuating Neuroinflammation via HMGB1/TLR4- and TNF-α/TNFR1-Mediated NF-κB Activation.

Inflammation is a potential factor in the pathophysiology of depression. A traditional Chinese herbal medicine, arctiin, and its aglycone, arctigenin, are the major bioactive components in Fructus arctii and exhibit neuroprotective and anti-inflammatory activities. Arctigenin has been reported to have antidepressant-like effects. However, the antidepressant-like effects of arctiin, its precursor, remain unknown. In this study, we investigated the antidepressant-like effects of arctiin and its underlying mechanisms by in vivo and in vitro experiments in mice. Our results showed that arctiin significantly attenuated sucrose consumption and increased the immobility time in tail suspension and forced swimming tests. Arctiin decreased neuronal damage in the prefrontal cortex (PFC) of the brain. Arctiin also attenuated the levels of three inflammatory mediators, indoleamine 2,3-dioxygenase, 5-hydroxytryptamine, and dopamine, that were elevated in the PFC or serum of chronic unpredictable mild stress (CUMS)-exposed mice. Arctiin reduced excessive activation of microglia and neuroinflammation by reducing high mobility group box 1 (HMGB1)/toll-like receptor 4 (TLR4)- and tumor necrosis factor-α (TNF-α)/TNF receptor 1 (TNFR1)-mediated nuclear factor-kappa B (NF-κB) activation in the PFC of CUMS-exposed mice and HMGB1- or TNF-α-stimulated primary cultured microglia. These findings demonstrate that arctiin ameliorates depression by inhibiting the activation of microglia and inflammation via the HMGB1/TLR4 and TNF-α/TNFR1 signaling pathways.

Metabonomic analysis of plasma biochemical changes in pyrexia rats after treatment with Gegenqinlian decoction, aspirin and itraconazole by UHPLC-FT-ICR-MS.

A metabonomic approach involving an ultrahigh-performance liquid chromatography combined with Fourier transform ion cyclotron resonance mass spectrometry (UHPLC-FT-ICR-MS) was used to investigate the changes in the endogenous metabolites in the plasma of rats with yeast-induced pyrexia treated with Gegenqinlian decoction (GQLD), aspirin and itraconazole. The differences in the small molecule profiles of treatment using traditional Chinese medicine, etiological treatment and symptomatic treatment were elucidated. Thirty-six plasma metabolites were identified or putatively identified, and the effects of the three medicines on the thirty-six metabolites were studied. Their metabolic pathways indicated that GQLD, aspirin and itraconazole ameliorated the rats with yeast-induced pyrexia predominantly by regulating the metabolisms of phospholipid, sphingolipid, fatty acid oxidation, fatty acid amides, amino acid and glycerolipid in vivo. The pharmacodynamics and metabonomic results showed that the three medicines exhibited the therapeutic effects on pyrexia by regulating the perturbations of multiple metabolisms. The study provided a scientific basis for an in-depth understanding of the therapeutic effects of GQLD, aspirin and itraconazole on rats with yeast-induced pyrexia.

Rapid characterization of chemical constituents of Gansuibanxia decoction by UHPLC-FT-ICR-MS analysis.

Gansuibanxia decoction (GSBXD) is one of the most famous traditional Chinese medicine (TCM). It is a herbal formula used for treating hydrops, such as cancerous ascites, pleural effusion, pericardial effusion, etc. However, the chemical constituents of GSBXD were still unclear. In this study, an UHPLC-FT-ICR-MS method was established and applied to the separation and characterization of the chemical constituents of GSBXD. A total of 62 components were chemically defined or tentatively identified, including diterpenoids, triterpenoids, flavonoids, monoterpene glycosides and alkaloids. The results is meaningful for a better understanding of the material basis of GSBXD and can be the basis for its further in vitro and in vivo studies.

Investigation of the mechanism of incompatible herb pair gansui-gancao-induced hepatotoxicity and nephrotoxicity and the attenuated effect of gansuibanxia decoction by UHPLC-FT-ICR-MS-based plasma metabonomic analysis.

Gansui-Gancao is one of the "eighteen incompatible herb pairs" which was recorded 2000 years ago according to TCM (Traditional Chinese Medicine) theory for their toxicity when using together. Nevertheless, Gansuibanxia decoction contained the herb pair have satisfactory effect on the treatment of cancerous ascites, pericardial effusion, etc. The present study aimed to investigate the mechanism of the incompatibility of Gansui-Gancao and the compatibility of Gansuibanxia decoction using UHPLC-FT-ICR-MS in a metabonomic perspective. Rats were divided into four groups administrated with different herb combination extracts for successive 14 days. Orthogonal partial least squares-discriminant analysis (OPLS-DA) was used to plot the metabolic state and screen the potential biomarkers in plasma. A total of 20 biomarkers contributed to the separation of Gansui-Gancao group and control group were tentatively identified mainly involved in 7 metabolic pathways related to hepatotoxicity and nephrotoxicity. The contents of these biomarkers were adjusted to normal levels in Gansuibanxia decoction group. Thus, the results of our study reveled the mechanism of the incompatibility of Gansui-Gancao and the compatibility of Gansuibanxia decoction in a metabonomic perspective and it's valuable for better understanding the "eighteen incompatible madicaments" of TCM theory.